transferrin

Summary

Gene Symbol: transferrin
Description: transferrin
Alias: HEL-S-71p, PRO1557, PRO2086, TFQTL1, serotransferrin, beta-1 metal-binding globulin, epididymis secretory sperm binding protein Li 71p, siderophilin
Species: human

Top Publications

  1. doi Carbon monoxide (CO)-releasing molecule-derived CO regulates tissue factor and plasminogen activator inhibitor type 1 in human endothelial cells
    Keiko Maruyama
    Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
    Thromb Res 130:e188-93. 2012
  2. pmc Nox2 and Rac1 regulate H2O2-dependent recruitment of TRAF6 to endosomal interleukin-1 receptor complexes
    Qiang Li
    Department of Anatomy and Cell Biology, College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA
    Mol Cell Biol 26:140-54. 2006
  3. ncbi The mechanism of iron release from the transferrin-receptor 1 adduct
    Miryana Hemadi
    ITODYS Interfaces, Traitements, Organisation et Dynamique des Systemes, Université Paris 7 CNRS UMR 7086, 1 rue Guy de la Brosse, 75005 Paris, France
    J Mol Biol 358:1125-36. 2006
  4. pmc Changes in brain gene expression shared by scrapie and Alzheimer disease
    J R Duguid
    Geriatric Research, Education and Clinical Center, Edith N Rogers Memorial Veterans Hospital, Bedford, MA 01730
    Proc Natl Acad Sci U S A 86:7260-4. 1989
  5. ncbi Human transferrin (Tf): a single mutation at codon 570 determines Tf C1 or Tf C2 variant
    K Namekata
    Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan
    Hum Genet 100:457-8. 1997
  6. pmc The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding
    J N Feder
    Progenitor, Inc formerly Mercator Genetics, Inc, 4040 Campbell Avenue, Menlo Park, CA 94025, USA
    Proc Natl Acad Sci U S A 95:1472-7. 1998
  7. ncbi Ligand-induced conformational change in transferrins: crystal structure of the open form of the N-terminal half-molecule of human transferrin
    P D Jeffrey
    Department of Biochemistry, Massey University, Palmerston North, New Zealand
    Biochemistry 37:13978-86. 1998
  8. ncbi Alternative splicing prevents transferrin secretion during differentiation of a human oligodendrocyte cell line
    G A de Arriba Zerpa
    Unité d Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France
    J Neurosci Res 61:388-95. 2000
  9. ncbi Human transferrin G277S mutation: a risk factor for iron deficiency anaemia
    P L Lee
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Br J Haematol 115:329-33. 2001
  10. ncbi Association study between late-onset Alzheimer's disease and the transferrin gene polymorphisms in Chinese
    Peng Zhang
    Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101 Beijing, China
    Neurosci Lett 349:209-11. 2003

Research Grants

  1. Brain Development on Adults with Schizophrenia
    George Bartzokis; Fiscal Year: 2008
  2. Iron Status: A Pathway Analysis in Multiple Ethnicities
    Christine McLaren; Fiscal Year: 2009
  3. IRON BINDING PROTEINS AND CONTROL OF IRON METABOLISM
    Philip Aisen; Fiscal Year: 2001
  4. FORMATION AND SURVIVAL OF RED BLOOD CELLS
    Ernest Beutler; Fiscal Year: 2001
  5. IRON TRANSPORT IN MAMMALIAN CELLS
    Philip Aisen; Fiscal Year: 2003
  6. A Mouse Model of Gaucher Disease
    Ernest Beutler; Fiscal Year: 2005
  7. SEARCH FOR NOVEL EARLY-ONSET ALZHEIMER'S GENES
    Lars Bertram; Fiscal Year: 2007

Detail Information

Publications127 found, 100 shown here

  1. doi Carbon monoxide (CO)-releasing molecule-derived CO regulates tissue factor and plasminogen activator inhibitor type 1 in human endothelial cells
    Keiko Maruyama
    Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
    Thromb Res 130:e188-93. 2012
    ..Additionally, we examined the mechanism by which CO exerts its effects...
  2. pmc Nox2 and Rac1 regulate H2O2-dependent recruitment of TRAF6 to endosomal interleukin-1 receptor complexes
    Qiang Li
    Department of Anatomy and Cell Biology, College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA
    Mol Cell Biol 26:140-54. 2006
    ..The identification of Nox-active endosomes helps explain how subcellular compartmentalization of redox signals can be used to direct receptor activation from the plasma membrane...
  3. ncbi The mechanism of iron release from the transferrin-receptor 1 adduct
    Miryana Hemadi
    ITODYS Interfaces, Traitements, Organisation et Dynamique des Systemes, Université Paris 7 CNRS UMR 7086, 1 rue Guy de la Brosse, 75005 Paris, France
    J Mol Biol 358:1125-36. 2006
    ..determination in cell-free assays of the mechanism of iron release from the N-lobe and C-lobe of human serum transferrin in interaction with intact transferrin receptor 1 at 4.3< or =pH< or =6.5...
  4. pmc Changes in brain gene expression shared by scrapie and Alzheimer disease
    J R Duguid
    Geriatric Research, Education and Clinical Center, Edith N Rogers Memorial Veterans Hospital, Bedford, MA 01730
    Proc Natl Acad Sci U S A 86:7260-4. 1989
    ..DNA sequence analysis has shown that these two recombinants represent the genes for sulfated glycoprotein 2 and transferrin. The abundance of sulfated glycoprotein 2 RNA is increased in hippocampus from patients with Alzheimer disease ..
  5. ncbi Human transferrin (Tf): a single mutation at codon 570 determines Tf C1 or Tf C2 variant
    K Namekata
    Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan
    Hum Genet 100:457-8. 1997
    b>Transferrin (Tf) has many variants, as revealed by isoelectric focusing (IEF)...
  6. pmc The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding
    J N Feder
    Progenitor, Inc formerly Mercator Genetics, Inc, 4040 Campbell Avenue, Menlo Park, CA 94025, USA
    Proc Natl Acad Sci U S A 95:1472-7. 1998
    ..wild-type or mutant HFE proteins that both the wild-type and H63D HFE proteins form stable complexes with the transferrin receptor (TfR)...
  7. ncbi Ligand-induced conformational change in transferrins: crystal structure of the open form of the N-terminal half-molecule of human transferrin
    P D Jeffrey
    Department of Biochemistry, Massey University, Palmerston North, New Zealand
    Biochemistry 37:13978-86. 1998
    Serum transferrin binds ferric ions in the bloodstream and transports them to cells, where they are released in a process involving receptor-mediated endocytosis...
  8. ncbi Alternative splicing prevents transferrin secretion during differentiation of a human oligodendrocyte cell line
    G A de Arriba Zerpa
    Unité d Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France
    J Neurosci Res 61:388-95. 2000
    b>Transferrin, the iron-transport protein of vertebrate serum, is synthesized mainly in the liver, from which it is secreted into the blood...
  9. ncbi Human transferrin G277S mutation: a risk factor for iron deficiency anaemia
    P L Lee
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Br J Haematol 115:329-33. 2001
    Numerous polymorphisms of the transferrin gene result in a range of electrophoretic variants. We show that one of these mutations has a functional consequence...
  10. ncbi Association study between late-onset Alzheimer's disease and the transferrin gene polymorphisms in Chinese
    Peng Zhang
    Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 100101 Beijing, China
    Neurosci Lett 349:209-11. 2003
    To investigate the possible involvement of the transferrin (TF) gene polymorphism in the manifestation of Alzheimer's disease (AD), we analyzed the TF and apolipoprotein E (APOE) genotypes of 67 sporadic late-onset AD patients and 131 ..
  11. ncbi Structural reorganization of the transferrin C-lobe and transferrin receptor upon complex formation: the C-lobe binds to the receptor helical domain
    Rutao Liu
    Center for Synchrotron Biosciences, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 42:12447-54. 2003
    Human transferrin, a bilobal protein, with each lobe bearing a single iron-binding site, functions to transport iron into cells...
  12. ncbi Structure of the human transferrin receptor-transferrin complex
    Yifan Cheng
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Cell 116:565-76. 2004
    Iron, insoluble as free Fe(3+) and toxic as free Fe(2+), is distributed through the body as Fe(3+) bound to transferrin (Tf) for delivery to cells by endocytosis of its complex with transferrin receptor (TfR)...
  13. ncbi Transferrin receptor co-localizes and interacts with the hemochromatosis factor (HFE) and the divalent metal transporter-1 (DMT1) in trophoblast cells
    Yaron Gruper
    Department of Cell Research and Immunology, The George S Wise Faculty of Life Sciences, Tel Aviv University, Israel
    J Cell Physiol 204:901-12. 2005
    ..Based on previous and these data we suggest that the level of intracellular iron may regulate both TfR expression (on the post-transcriptional and the post-translational levels) and TfR trafficking/transcytosis in polarized cells...
  14. ncbi Tissue factor and coagulation factor VII levels during acute myocardial infarction: association with genotype and adverse events
    Gianluca Campo
    Department of Cardiology, University of Ferrara, 44100 Ferrara, Italy
    Arterioscler Thromb Vasc Biol 26:2800-6. 2006
    ....
  15. ncbi The G277S transferrin mutation does not affect iron absorption in iron deficient women
    Beatriz Sarria
    Department of Metabolism and Nutrition, Instituto del Frio, Spanish Council for Scientific Research CSIC, C Jose Antonio Novais 10, 28040 Madrid, Spain
    Eur J Nutr 46:57-60. 2007
    ..The G277S transferrin mutation has been implicated as a risk factor for iron deficiency in menstruating women...
  16. ncbi Association study between the transferrin gene and schizophrenia in the Japanese population
    Nobuhisa Maeno
    Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Neuroreport 18:517-20. 2007
    ..Of myelin and oligodendrocyte-related genes, a significant decrease in the mRNA levels of transferrin in schizophrenics has been reported by both microarray and quantitative polymerase chain reaction studies...
  17. pmc Variants in iron metabolism genes predict higher blood lead levels in young children
    Marianne R Hopkins
    Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
    Environ Health Perspect 116:1261-6. 2008
    ..Given the association between iron deficiency and lead absorption, we hypothesized that variants in iron metabolism genes would predict higher blood lead levels in young children...
  18. pmc Assessment of Alzheimer's disease case-control associations using family-based methods
    Brit Maren M Schjeide
    MassGeneral Institute for Neurodegenerative Disease MIND, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Neurogenetics 10:19-25. 2009
    ..Further fine-mapping and functional analyses are warranted to elucidate the potential biochemical mechanisms and epidemiological relevance of these genes...
  19. pmc Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels
    Beben Benyamin
    Queensland Institute of Medical Research, Brisbane 4029, Australia
    Am J Hum Genet 84:60-5. 2009
    ..We report the results from two GWASs for serum markers of iron status (serum iron, serum transferrin, transferrin saturation with iron, and serum ferritin), which are important in iron overload (e.g...
  20. pmc Iron metabolism genes, low-level lead exposure, and QT interval
    Sung Kyun Park
    Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan 48109, USA
    Environ Health Perspect 117:80-5. 2009
    ..oxidative effects of lead, we examined whether polymorphisms in iron metabolism genes [hemochromatosis (HFE), transferrin (TF) C2, and heme oxygenase-1 (HMOX-1)] increase susceptibility to the effects of lead on QT interval in 613 ..
  21. doi The role of transferrin receptor 1 and 2 in transferrin-bound iron uptake in human hepatoma cells
    Carly E Herbison
    The Univ of Western Australia, Fremantle Hospital, Australia
    Am J Physiol Cell Physiol 297:C1567-75. 2009
    b>Transferrin receptor (TFR) 1 and 2 are expressed in the liver; TFR1 levels are regulated by cellular iron levels while TFR2 levels are regulated by transferrin saturation...
  22. doi Computational structure models of apo and diferric transferrin-transferrin receptor complexes
    Tetsuya Sakajiri
    Department of Applied Chemistry, Tokyo University of Science, Shinjuku ku, Tokyo 162 8601, Japan
    Protein J 28:407-14. 2009
    Complexation of transferrin (Tf) and its receptor (TfR) is an essential event for iron uptake by the cell. Much data has been accumulated regarding Tf-TfR complexation, such as results from mutagenesis...
  23. pmc Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease
    J S K Kauwe
    Department of Psychiatry and Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Am J Med Genet B Neuropsychiatr Genet 153:955-9. 2010
    ..2004); J Med Genet 41:261-265] reported that epistatic interaction between rs1049296 (P589S) in the transferrin gene (TF) and rs1800562 (C282Y) in the hemochromatosis gene (HFE) results in significant association with risk ..
  24. pmc Properties of a homogeneous C-lobe prepared by introduction of a TEV cleavage site between the lobes of human transferrin
    Ashley N Steere
    Department of Biochemistry, University of Vermont, College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA
    Protein Expr Purif 72:32-41. 2010
    Essential to iron transport and delivery, human serum transferrin (hTF) is a bilobal glycoprotein capable of reversibly binding one ferric ion in each lobe (the N- and C-lobes)...
  25. pmc Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 6968, USA
    J Alzheimers Dis 20:333-41. 2010
    Prevalent gene variants involved in iron metabolism [hemochromatosis (HFE) H63D and transferrin C2 (TfC2)] have been associated with higher risk and earlier age at onset of Alzheimer's disease (AD), especially in men...
  26. doi Systematic analysis of candidate genes for Alzheimer's disease in a French, genome-wide association study
    Geoffroy Laumet
    INSERM U744, Lille, France
    J Alzheimers Dis 20:1181-8. 2010
    ..Of the genes showing nominal association in our cohorts, TFAM and CHRNB2 appear particularly interesting and warrant further genetic and functional follow-up analyses...
  27. pmc Gender and iron genes may modify associations between brain iron and memory in healthy aging
    George Bartzokis
    Department of Psychiatry and Biobehavioral Sciences, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 6968, USA
    Neuropsychopharmacology 36:1375-84. 2011
    ..prevalent allelic variants in genes encoding for iron metabolism proteins (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2))...
  28. pmc How the binding of human transferrin primes the transferrin receptor potentiating iron release at endosomal pH
    Brian E Eckenroth
    Department of Biochemistry, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405, USA
    Proc Natl Acad Sci U S A 108:13089-94. 2011
    Delivery of iron to cells requires binding of two iron-containing human transferrin (hTF) molecules to the specific homodimeric transferrin receptor (TFR) on the cell surface...
  29. pmc Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene
    Neda Jahanshad
    Laboratory of Neuroimaging, Department of Neurology, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 109:E851-9. 2012
    ..Specific genetic markers have been previously identified that influence levels of transferrin, the protein that transports iron throughout the body, in the blood and brain...
  30. pmc Structural basis for iron piracy by pathogenic Neisseria
    Nicholas Noinaj
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 483:53-8. 2012
    ..Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane...
  31. doi Molecular dynamics simulations of iron- and aluminum-loaded serum transferrin: protonation of Tyr188 is necessary to prompt metal release
    J I Mujika
    Kimika Fakultatea, Euskal Herriko Unibertsitatea UPV EHU and Donostia International Physics Center, PK 1072, 20080 Donostia, Euskadi, Spain
    Biochemistry 51:7017-27. 2012
    Serum transferrin (sTf) carries iron in blood serum and delivers it into cells by receptor-mediated endocytosis. The protein can also bind other metals, including aluminum...
  32. doi Subcellular localization of tissue factor and human coronary artery smooth muscle cell migration
    E Pena
    Cardiovascular Research Center, CSIC ICCC, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona CIBEROBN Pathophysiology of Obesity and Nutrition, Barcelona Cardiovascular Research Chair, UAB, Barcelona, Spain
    J Thromb Haemost 10:2373-82. 2012
    ..Tissue factor (TF) is the most relevant physiological trigger of thrombosis. Additionally TF is a transmembrane receptor with cell signaling functions...
  33. doi An association of transferrin gene polymorphism and serum transferrin levels with age-related macular degeneration
    Daniel Wysokinski
    Department of Molecular Genetics, University of Lodz, Pomorska 141 143, 90 236 Lodz, Poland
    Exp Eye Res 106:14-23. 2013
    ..In the present work we investigated the association between four polymorphisms of the transferrin gene (rs8177178; rs8177179; rs4481157; rs1130459) and AMD in dependence on the transferrin protein and iron ..
  34. ncbi Intracellular and surface expression of the HIV-1 coreceptor CXCR4/fusin on various leukocyte subsets: rapid internalization and recycling upon activation
    R Forster
    Max Delbruck Center for Molecular Medicine, Berlin Buch, Germany
    J Immunol 160:1522-31. 1998
    ..Therefore, receptor internalization and recycling may regulate the functional interaction of the receptor with envelope proteins during an initial step of HIV-1 infection...
  35. ncbi Apotransferrin decreases migration and enhances differentiation of oligodendroglial progenitor cells in an in vitro system
    Pablo M Paez
    Instituto de Quimica y Fisicoquimica Biologica, UBA CONICET, Universidad de Buenos Aires, Argentina
    Dev Neurosci 24:47-58. 2002
    ..This effect was not observed when an antibody against the transferrin receptor was added...
  36. ncbi The position of arginine 124 controls the rate of iron release from the N-lobe of human serum transferrin. A structural study
    Ty E Adams
    Department of Biochemistry, University of Vermont, College of Medicine, Burlington, Vermont 05405, USA
    J Biol Chem 278:6027-33. 2003
    Human serum transferrin (hTF) is a bilobal iron-binding and transport protein that carries iron in the blood stream for delivery to cells by a pH-dependent mechanism...
  37. ncbi Apotransferrin promotes the differentiation of two oligodendroglial cell lines
    Pablo M Paez
    Instituto de Química y Fisicoquímica Biológica IQUIFIB, UBA CONICET, Buenos Aires, Argentina
    Glia 46:207-17. 2004
    ..The results suggest that aTf can influence OLGc gene expression and differentiation through multiple mechanisms depending on the maturation of the cell...
  38. pmc Synergy between the C2 allele of transferrin and the C282Y allele of the haemochromatosis gene (HFE) as risk factors for developing Alzheimer's disease
    K J H Robson
    MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK
    J Med Genet 41:261-5. 2004
    ..There is evidence that iron may play a role in the pathology of Alzheimer's disease (AD). There may be genetic factors that contribute to iron deposition resulting in tissue damage thus exacerbating AD...
  39. pmc Organization of the human transferrin gene: direct evidence that it originated by gene duplication
    I Park
    Proc Natl Acad Sci U S A 82:3149-53. 1985
    We present the characterization of two overlapping human transferrin genomic clones isolated from a liver DNA library. The two clones represent a total length of 24 kilobase pairs and code for 70% of the protein...
  40. ncbi Molecular cloning and sequence analysis of cDNA for human transferrin
    G Uzan
    Biochem Biophys Res Commun 119:273-81. 1984
    A cDNA clone for human transferrin was identified from a human liver cDNA library by pre-screening with different ss-cDNA probes against length-fractionated liver mRNAs, positive hybridization-selection and nucleotide sequence analysis...
  41. ncbi Transferrin C2 variant does not confer a risk for Alzheimer's disease in Koreans
    K W Kim
    Department of Neuropsychiatry, Kyunggi Provincial Hospital for the Elderly, 17 Sangha ri, Koosung Myun, Yongin, Kyunggi Do, South Korea
    Neurosci Lett 308:45-8. 2001
    We analyzed the transferrin (TF) and apolipoprotein E (APOE) genotypes of 164 probable Alzheimer's disease (AD) patients and 239 cognitively normal elderly controls in Koreans...
  42. ncbi Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes
    Anne Simonsen
    Department of Biochemistry, The Norwegian Radium Hospital, Montebello, Oslo 0310, Norway
    J Cell Sci 117:4239-51. 2004
    ..By electron microscopy, similar structures can be found within autophagosomes. We propose that Alfy might target cytosolic protein aggregates for autophagic degradation...
  43. doi HFE association with transferrin receptor 2 increases cellular uptake of transferrin-bound iron
    Abdul Waheed
    Edward A Doisy Department of Biochemistry and Molecular Biology, Saint Louis University Liver Center, Saint Louis University School of Medicine, St Louis, MO 63104, USA
    Arch Biochem Biophys 474:193-7. 2008
    Mutations in either HFE or transferrin receptor 2 (TfR2) cause decreased expression of the iron regulatory hormone hepcidin and hemochromatosis...
  44. doi The impact of hemochromatosis mutations and transferrin genotype on gonadotropin serum levels in infertile men
    Alena Buretic-Tomljanovic
    Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Rijeka, Croatia
    Fertil Steril 91:1793-800. 2009
    ..To address the possibility that HFE mutations and TF gene polymorphism cause dysfunction of spermatogenesis and/or the hypothalamic-pituitary-gonadal axis via contribution to long-term iron overload in the testes and brain...
  45. pmc Definition of the residues required for the interaction between glycine-extended gastrin and transferrin in vitro
    Suzana Kovac
    Department of Surgery, University of Melbourne, Austin Health, Victoria, Australia
    FEBS J 276:4866-74. 2009
    b>Transferrin is the main iron transport protein found in the circulation, and the level of transferrin saturation in the blood is an important indicator of iron status...
  46. doi Investigation on the interaction between tamoxifen and human holo-transferrin: determination of the binding mechanism by fluorescence quenching, resonance light scattering and circular dichroism methods
    Sareh Sarzehi
    Department of Biology, Faculty of Sciences, Islamic Azad University Mashhad Branch, Rahnamaee Avenue, Mashhad, Iran
    Int J Biol Macromol 47:558-69. 2010
    The interaction between tamoxifen (TMX) and human serum transferrin (HTF) was for the first time studied at varying pH values by fluorescence spectroscopy, circular dichroism (CD) and resonance light scattering (RLS)...
  47. pmc Genome-wide association study identifies genetic loci associated with iron deficiency
    Christine E McLaren
    Department of Epidemiology, University of California Irvine, Irvine, California, United States of America
    PLoS ONE 6:e17390. 2011
    ..2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF) gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr...
  48. doi HFE mutations and transferrin C1/C2 polymorphism among Croatian patients with schizophrenia and schizoaffective disorder
    Alena Buretic-Tomljanovic
    Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Brace Branchetta 20, 51000 Rijeka, Croatia
    Mol Biol Rep 39:2253-8. 2012
    ..this study was to investigate the possible influence of hemochromatosis gene mutations (HFE-C282Y and H63D) and transferrin gene C2 variant (TF-C2) on susceptibility to schizophrenia and schizoaffective disorder and/or age at first ..
  49. doi Retinal function and structure in the hypotransferrinemic mouse
    Michal Lederman
    Department of Ophthalmology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Invest Ophthalmol Vis Sci 53:605-12. 2012
    The iron carrier transferrin is expressed at remarkably high levels in normal retinas and is upregulated during retinal degeneration...
  50. doi Intronic SNP rs3811647 of the human transferrin gene modulates its expression in hepatoma cells
    R Blanco-Rojo
    Department of Metabolism and Nutrition, Institute of Food Science, Techonology and Nutrition, Spanish National Research Council, CSIC, Madrid, Spain
    Nutr Hosp 27:2142-5. 2012
    b>Transferrin (Tf) exerts a crucial function in the maintenance of systemic iron homeostasis. The expression of the Tf gene is controlled by transcriptional mechanism, although little is known about genetic factors influence.
  51. pmc Polymorphism of the transferrin gene in eye diseases: keratoconus and Fuchs endothelial corneal dystrophy
    Katarzyna A Wójcik
    Department of Molecular Genetics, University of Lodz, Pomorska 141 143, 90 236 Lodz, Poland
    Biomed Res Int 2013:247438. 2013
    ..Iron may promote the stress by the Fenton reaction, so its homeostasis should be strictly controlled. Transferrin is essential for iron homeostasis because it transports iron from plasma into cells...
  52. doi Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin
    Vishant Mahendra Boradia
    National Institute of Pharmaceutical Education and Research NIPER, Phase X, Sector 67, SAS Nagar, Punjab 160062, India
    Nat Commun 5:4730. 2014
    ..by synthesizing iron-binding molecules known as siderophores and by recruiting a host iron-transport protein, transferrin, to the phagosome. The siderophores extract iron from transferrin and transport it into the bacterium...
  53. pmc Enhanced tissue factor expression by blood eosinophils from patients with hypereosinophilia: a possible link with thrombosis
    Massimo Cugno
    Dipartimento di Fisiopatologia Medico Chirurgica e dei Trapianti, Universita degli Studi di Milano, Milano, Italy Medicina Interna, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, Milano, Italy
    PLoS ONE 9:e111862. 2014
    ..77 (19.22-25.05). Our results indicate that human blood eosinophils contain variable amounts of TF. The higher TF expression in patients with hypereosinophilic disorders may contribute to increase the thrombotic risk. ..
  54. doi Common Variants and Haplotypes in the TF, TNF-α, and TMPRSS6 Genes Are Associated with Iron Status in a Female Black South African Population
    Wanjiku N Gichohi-Wainaina
    Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
    J Nutr 145:945-53. 2015
    ..It is unknown whether single nucleotide polymorphisms (SNPs), associated with iron status in European and Asian populations, have the same relation within the African population...
  55. doi Subgroup differences in 'brain-type' transferrin and α-synuclein in Parkinson's disease and multiple system atrophy
    Akioh Yoshihara
    Departments of Neurology
    J Biochem 160:87-91. 2016
    Two transferrin (Tf) glycan-isoforms were previously found in cerebrospinal fluid (CSF); one appears to be derived from serum (Tf-2) and the other from choroid plexus, a CSF-producing tissue (Tf-1)...
  56. doi A unique N-glycan on human transferrin in CSF: a possible biomarker for iNPH
    Satoshi Futakawa
    Department of Biochemistry, Fukushima Medical University School of Medicine, Fukushima, Japan
    Neurobiol Aging 33:1807-15. 2012
    ..On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we found two transferrin isoforms: one had a unique N-glycan (Tf-1) whereas the other had N-glycan similar to that of serum transferrin (..
  57. doi Na+/H+ exchanger isoform 6 (NHE6/SLC9A6) is involved in clathrin-dependent endocytosis of transferrin
    Lou Xinhan
    Department of Biological Sciences, Graduate School of Science, Osaka University, Machikaneyama cho 1 1, Toyonaka City, Osaka, Japan
    Am J Physiol Cell Physiol 301:C1431-44. 2011
    ..Uptake of transferrin was also decreased...
  58. doi Titanium preferential binding sites in human serum transferrin at physiological concentrations
    Yoana Nuevo-Ordóñez
    Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain
    Metallomics 3:1297-303. 2011
    Serum transferrin (Tf) is an iron binding glycoprotein that plays a central role in the metabolism of this essential metal but it also binds other metal ions...
  59. doi TMPRSS6, but not TF, TFR2 or BMP2 variants are associated with increased risk of iron-deficiency anemia
    Peng An
    Key Laboratory of Nutrition and Metabolism, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
    Hum Mol Genet 21:2124-31. 2012
    ..Variants rs3811647 in TF and rs7385804 in TFR2 were associated with reduced SI, serum transferrin and transferrin saturation levels; however, these variants were not associated with iron deficiency or anemia ..
  60. pmc Structure-based mutagenesis reveals critical residues in the transferrin receptor participating in the mechanism of pH-induced release of iron from human serum transferrin
    Ashley N Steere
    Department of Biochemistry, University of Vermont, College of Medicine, Burlington, Vermont 05405, United States
    Biochemistry 51:2113-21. 2012
    The recent crystal structure of two monoferric human serum transferrin (Fe(N)hTF) molecules bound to the soluble portion of the homodimeric transferrin receptor (sTFR) has provided new details about this binding interaction that dictates ..
  61. doi Lower tissue factor inhibition in patients with ST segment elevation than in patients with non ST elevation acute myocardial infarction
    Jaume Figueras
    Unitat Coronaria, Area del Cor, Hospital Universitari Vall d Hebron, Barcelona, Spain
    Thromb Res 130:458-62. 2012
    ..We hypothesize, however, that STEMI patients may present lower tissue factor plasma inhibition to partly account for their more persistent coronary thrombotic occlusion...
  62. doi Transferrin polymorphism and opportunistic infections in HIV-infected women in Rwanda
    Florence Masaisa
    Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium
    Acta Haematol 128:100-6. 2012
    We investigated the prevalence of opportunistic infections in HIV-infected women according to transferrin (TF) phenotype.
  63. pmc The immunobiology of apotransferrin in type 1 diabetes
    K Mangano
    Department of Bio Medical Sciences, Via Androne 83, 95124, Catania, Italy
    Clin Exp Immunol 169:244-52. 2012
    The transferrin (Tf) family of iron binding proteins includes important endogenous modulators of the immune function that may modulate autoimmune diseases...
  64. ncbi The human transferrin gene: 5' region contains conserved sequences which match the control elements regulated by heavy metals, glucocorticoids and acute phase reaction
    G S Adrian
    Gene 49:167-75. 1986
    b>Transferrin is a major plasma protein that transports iron to proliferating cells throughout the body. A clone containing the 5' region of the human transferrin gene has been isolated and characterized...
  65. ncbi Complete structure of the human transferrin gene. Comparison with analogous chicken gene and human pseudogene
    E Schaeffer
    Unite de Biochimie Cellulaire, Institut Pasteur, Paris, France
    Gene 56:109-16. 1987
    The complete structure of the human transferrin gene is presented. This gene has a total size of about 33.5 kb and is organized in 17 exons separated by 16 introns. The chicken ovotransferrin gene has a size of 10...
  66. ncbi Human transferrins C and D-Chi: an amino acid difference
    A C Wang
    Biochem Genet 1:55-9. 1967
  67. ncbi [Congenital atransferrinemia in a 11-month-old child]
    J Cap
    Cesk Pediatr 23:1020-5. 1968
  68. ncbi Exon/intron structure of the human transferrin receptor gene
    P Evans
    Department of Pathology, University of Iowa College of Medicine, Iowa City, USA
    Gene 199:123-31. 1997
    A PCR-based intron jumping strategy has been utilized to investigate the exon/intron structure of the human transferrin receptor gene and determine the sequences of exon/intron junctions...
  69. ncbi Two high-resolution crystal structures of the recombinant N-lobe of human transferrin reveal a structural change implicated in iron release
    R T MacGillivray
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
    Biochemistry 37:7919-28. 1998
    The N-lobe of human serum transferrin (hTF/2N) has been expressed in baby hamster kidney cells and crystallized in both orthorhombic (P212121) and tetragonal (P41212) space groups. Both crystal forms diffract to high resolution (1...
  70. ncbi X-ray crystallography and mass spectroscopy reveal that the N-lobe of human transferrin expressed in Pichia pastoris is folded correctly but is glycosylated on serine-32
    M C Bewley
    Institute of Molecular Biosciences, College of Sciences, Massey University, Palmerston North, New Zealand
    Biochemistry 38:2535-41. 1999
    The ferric form of the N-lobe of human serum transferrin (Fe(III)-hTF/2N) has been expressed at high levels in Pichia pastoris...
  71. ncbi Molecular characterization of a case of atransferrinemia
    E Beutler
    The Scripps Research Institute, La Jolla, CA92037, USA
    Blood 96:4071-4. 2000
    ..We determined the sequences flanking the exons of the human transferrin gene and sequenced all of the exons and some of the flanking regions of the patient's DNA and that of her ..
  72. ncbi Truncated brush border myosin I affects membrane traffic in polarized epithelial cells
    A Durrbach
    CNRS ERS 1984, 19 rue Guy Moquet 94801 Villejuif, France
    Traffic 1:411-24. 2000
    ..We observed that depolymerization of actin filaments using latrunculin A decreases the rate of transferrin recycling to the basolateral plasma membrane of Caco-2 cells, and increases its delivery to the apical plasma ..
  73. ncbi Identification of 96 single nucleotide polymorphisms in eight genes involved in iron metabolism: efficiency of bioinformatic extraction compared with a systematic sequencing approach
    V Douabin-Gicquel
    Département de Biochimie et Biologie Moléculaire, et UMR6061 CNRS, Faculte de Medecine, 2 Avenue du Pr Léon Bernard CS34317, 35043 Rennes Cedex, France
    Hum Genet 109:393-401. 2001
    ..The average distance between the SNPs and minor allele frequencies were higher than reported by others authors; this discrepancy may reflect the nature of the genes studied and the ethnic homogeneity of our test population...
  74. ncbi Molecular analysis of the transferrin gene in a patient with hereditary hypotransferrinemia
    Midori Asada-Senju
    Department of Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Beppu, Oita, Japan
    J Hum Genet 47:355-9. 2002
    ..from severe anemia and growth retardation and was diagnosed on the basis of an extremely low level of serum transferrin (TF)...
  75. ncbi Presence of alpha1-antitrypsin and transferrin in human follicular fluid--correlation with fertilization
    Vassiliki Aleporou-Marinou
    Department of Biology, University of Athens, Panepistimiopolis 15701, Athens, Greece
    Comp Biochem Physiol B Biochem Mol Biol 133:105-11. 2002
    ..of approximately 50 kDa and 80 kDa with N-terminal sequences similar to those of alpha1-antitrypsin (a1AT) and transferrin indicating that they are identical to or highly homologous to these proteins...
  76. ncbi Complexation of ytterbium to human transferrin and its uptake by K562 cells
    Xiu Lian Du
    Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, China
    Eur J Biochem 269:6082-90. 2002
    ..Lanthanide cations are similar to ferric ions with regard to transferrin binding, suggesting transferrin-receptor mediated transport is possible; however, this has not yet been ..
  77. ncbi Function and therapeutic development of apotransferrin
    Jaakko Parkkinen
    Finnish Red Cross Blood Transfusion Service, Helsinki, Finland
    Vox Sang 83:321-6. 2002
  78. ncbi The effects of ethanol on the glycosylation of human transferrin
    C Flahaut
    UMR 8576 du CNRS, Laboratoire de Glycobiologie Structurale et Fonctionnelle, Et Ifr 118 Ustl, 59655, Villeneuve d Ascq, France
    Glycobiology 13:191-8. 2003
    Appearance of a hyposialylated transferrin fraction in the plasma during chronic alcohol exposure is a well-known phenomenon, and it represents the best available marker of chronic alcohol consumption...
  79. pmc Proteomic and postproteomic characterization of keratan sulfate-glycanated isoforms of thyroglobulin and transferrin uniquely elaborated by papillary thyroid carcinomas
    Gaetano Magro
    Department F G Ingrassia, Section of Anatomic Pathology, University of Catania, Catania, Italy
    Am J Pathol 163:183-96. 2003
    ..approach revealed that the PTC-specific KS-bearing macromolecules were unique glycoforms of thyroglobulin and transferrin. Combined, reciprocal immunoprecipitation and Western blotting further indicated that the former glycoform ..
  80. ncbi Transcriptional regulation of the human transferrin gene by GADD153 in hepatoma cells
    Kyung Ran You
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Institute for Medical Science, Chonbuk National University Medical School and Hospital, Chonju, Chonbuk, South Korea
    Hepatology 38:745-55. 2003
    ..Among them, we further verified that the expression of transferrin (Tf), which is a negative acute-phase protein and is essential to cell survival as a growth factor, was highly ..
  81. ncbi Transferrin C2 variant does confer a risk for Alzheimer's disease in caucasians
    Pamela Zambenedetti
    Pathology Division and Brain Bank, General Hospital, Dolo Venice, Italy
    J Alzheimers Dis 5:423-7. 2003
    ..Previous studies reported higher transferrin C2 allele frequencies in Alzheimer's disease compared with normal controls...
  82. ncbi Molecular characterization of a third case of human atransferrinemia
    A S Knisely
    Blood 104:2607. 2004
  83. ncbi Soluble transferrin receptor and mutations in hemochromatosis and transferrin genes in a general Catalan population
    Victória Bérez
    Centre de Recerca Biomedica, Hospital Universitari de Sant Joan, Institut de Recerca en Ciències de la Salut, C Sant Joan s n, 43201 Reus, Catalunya, Spain
    Clin Chim Acta 353:205-8. 2005
    The measurement of soluble transferrin receptor (sTfR) has been proposed as a valuable marker of erythropoietic activity and iron status...
  84. ncbi The C2 variant of human serum transferrin retains the iron binding properties of the native protein
    Paolo Zatta
    CNR Institute for Biomedical Technologies, Metalloproteins Unit, Department of Biology, University of Padova, Vle G Colombo, 3, 3512 Padova, Italy
    Biochim Biophys Acta 1741:264-70. 2005
    The tryptic digests of blood samples obtained from transferrin C1 and C2 (TfC 1 and TfC2 hereafter) genotypes were analysed by Liquid Chromatography coupled to Electrospray Mass Spectrometry (LC/ESI--MS/MS)...
  85. ncbi Association study of the G258S transferrin gene polymorphism and Parkinson's disease in the Spanish population
    Mario Ezquerra
    J Neurol 252:1269-70. 2005
  86. ncbi Aluminum exposure affects transferrin-dependent and -independent iron uptake by K562 cells
    Gladys Pérez
    Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellon II, Piso 4, Ciudad Universitaria, Ciudad de Buenos Aires C1428EHA, Argentina
    Biochim Biophys Acta 1745:124-30. 2005
    Aluminum (Al) and iron (Fe) share several physicochemical characteristics and they both bind to transferrin (Tf), entering the cell via Tf receptors (TfR)...
  87. ncbi Serum level of sialic acid (SA) and carbohydrate-deficient transferrin (CDT) in type 2 diabetes mellitus with microvascular complications
    Bogdan Cylwik
    Department of Biochemical Diagnostics, Medical University, Bialystok, Poland
    J Clin Lab Anal 20:68-73. 2006
    Sialic acid (SA) is responsible for the composition of different isoforms of transferrin and is reported to be a marker of microvascular complications in type 2 diabetes mellitus...
  88. pmc Iron genes, iron load and risk of Alzheimer's disease
    D J Lehmann
    J Med Genet 43:e52. 2006
    Compound heterozygotes of the haemochromatosis gene (HFE) variants, H63D and C282Y, have raised transferrin saturation compared with that in the wild type...
  89. pmc Biological variability of transferrin saturation and unsaturated iron-binding capacity
    Paul C Adams
    Department of Medicine, University Hospital, London, Ontario, Canada
    Am J Med 120:999.e1-7. 2007
    b>Transferrin saturation is widely considered the preferred screening test for hemochromatosis. Unsaturated iron-binding capacity has similar performance at lower cost...
  90. ncbi Polymorphisms of Transferrin gene are associated with schizophrenia in Chinese Han population
    Mei Qu
    Key laboratory for Mental Health, Ministry of Health, Institute of Mental Health, Peking University, 51 Hua Yuan Bei Road, Beijing 100083, China
    J Psychiatr Res 42:877-83. 2008
    ..b>Transferrin (TF), an iron transport glycoprotein playing an important role in synthesis of myelin and the development of ..
  91. doi Genetic variants of transferrin in cystic fibrosis
    E Marklova
    Department of Pediatrics, Charles University in Prague, University Hospital in Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic
    J Inherit Metab Dis 31:457-61. 2008
    Genetic polymorphism of serum transferrin (Tf) was studied in order to differentiate between protein genetic variants and congenital disorders of glycosylation (CDG), further focusing on unusual findings.
  92. doi Atypical serum transferrin isoform distribution in liver cirrhosis studied by HPLC, capillary electrophoresis and transferrin genotyping
    Torsten Arndt
    Bioscientia Institut fuer Medizinische Diagnostik GmbH, Ingelheim, Germany
    Clin Chim Acta 394:42-6. 2008
    ..We describe a currently unknown disialotransferrin-trisialotransferrin-bridging phenomenon (di-tri-bridge) appearing with high prevalence in serum from liver cirrhosis patients...
  93. pmc The protective role of transferrin in Müller glial cells after iron-induced toxicity
    Emilie Picard
    INSERM, U872, Paris, France
    Mol Vis 14:928-41. 2008
    b>Transferrin (Tf) expression is enhanced by aging and inflammation in humans. We investigated the role of transferrin in glial protection.
  94. pmc Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta
    John S K Kauwe
    Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
    Neurogenetics 10:13-7. 2009
    ....
  95. doi Tissue factor and cancer
    Chloe Milsom
    Henderson Research Centre, McMaster University, Hamilton, Ont, Canada
    Pathophysiol Haemost Thromb 36:160-76. 2008
    ..The efficacy and safety of such approaches still awaits clinical verification...
  96. doi Tissue factor gene polymorphisms and haplotypes and the risk of ischemic vascular events: four studies and a meta-analysis
    M de Gaetano
    Laboratory of Genetic and Environmental Epidemiology, RE ARTU Research Laboratories John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
    J Thromb Haemost 7:1465-71. 2009
    ..We investigated the role of genetic polymorphisms and haplotypes of the TF gene in the risk of ischemic vascular disease...
  97. pmc A loop in the N-lobe of human serum transferrin is critical for binding to the transferrin receptor as revealed by mutagenesis, isothermal titration calorimetry, and epitope mapping
    Anne B Mason
    Department of Biochemistry, College of Medicine, University of Vermont, 89 Beaumont Avenue, Burlington, VT 05405, USA
    J Mol Recognit 22:521-9. 2009
    b>Transferrin (TF) is a bilobal transport protein that acquires ferric iron from the diet and holds it tightly within the cleft of each lobe (thereby preventing its hydrolysis)...
  98. pmc Human growth hormone-transferrin fusion protein for oral delivery in hypophysectomized rats
    Nurmamet Amet
    Department of Pharmacology and Pharmaceutical Sciences, University of Southern California School of Pharmacy, PSC 404B, 1985 Zonal Avenue, Los Angeles, CA 90089 9121, USA
    J Control Release 141:177-82. 2010
    b>Transferrin (Tf)-based recombinant fusion protein approach was investigated to achieve oral delivery for human growth hormone (hGH)...
  99. pmc Excited-state lifetime studies of the three tryptophan residues in the N-lobe of human serum transferrin
    Nicholas G James
    Department of Biochemistry, University of Vermont, College of Medicine, Burlington, Vermont 05405, USA
    Protein Sci 19:99-110. 2010
    The energy transfer from the three Trp residues at positions 8, 128, and 264 within the human serum transferrin (hTF) N-lobe to the ligand to metal charge transfer band has been investigated by monitoring changes in Trp fluorescence ..
  100. doi Human MRCKalpha is regulated by cellular iron levels and interferes with transferrin iron uptake
    Radek Cmejla
    Institute of Hematology and Blood Transfusion, Department of Cell Physiology, U Nemocnice 1, Prague 128 20, Czech Republic
    Biochem Biophys Res Commun 395:163-7. 2010
    ..Here we report that MRCKalpha protein expression is also regulated by iron levels; MRCKalpha colocalizes with transferrin (Tf)-loaded transferrin receptors (TfR), and attenuation of MRCKalpha expression by a short hairpin RNA ..

Research Grants7

  1. Brain Development on Adults with Schizophrenia
    George Bartzokis; Fiscal Year: 2008
    ..This will change our concept of how we could treat this illness, the feasibility of changing its lifelong course, and would encourage the development of novel pharmacologic interventions to improve myelination. [unreadable] [unreadable]..
  2. Iron Status: A Pathway Analysis in Multiple Ethnicities
    Christine McLaren; Fiscal Year: 2009
    ..Potential study results could be used to identify individuals at risk for iron deficiency and to develop innovative prevention and treatment strategies. ..
  3. IRON BINDING PROTEINS AND CONTROL OF IRON METABOLISM
    Philip Aisen; Fiscal Year: 2001
    ..Human transferrin, the major interest of this research, serves in the circulatory transport of iron for cellular needs...
  4. FORMATION AND SURVIVAL OF RED BLOOD CELLS
    Ernest Beutler; Fiscal Year: 2001
    ..Should these point mutations fail to alter gene transcription, a search will be made for other potential mutations in linkage disequilibrium with the known -5,-8 and -24 polymorphisms, by sequencing upstream through the promotor. ..
  5. IRON TRANSPORT IN MAMMALIAN CELLS
    Philip Aisen; Fiscal Year: 2003
    ..are: Project 1: Mechanisms of cellular iron uptake from transferring focuses on cellular iron acquisition from transferrin by receptor-independent routes, and also includes studies of transferrin-transferrin receptor interactions (in ..
  6. A Mouse Model of Gaucher Disease
    Ernest Beutler; Fiscal Year: 2005
    ..In particular, electron microscopy and light microscopy will be used to attempt to demonstrate the development of Gaucher cells in the chimeric mice. ..
  7. SEARCH FOR NOVEL EARLY-ONSET ALZHEIMER'S GENES
    Lars Bertram; Fiscal Year: 2007
    ..While we have devised a strategy that integrates the best available methods to identify complex disease genes, we will routinely adjust our strategy to account for methodologic advances in this rapidly evolving field. ..